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Health Technology Assessment... Mar 2022Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded...
BACKGROUND
Convulsive status epilepticus is defined as ≥ 5 minutes of either continuous seizure activity or repetitive seizures without regaining consciousness. It is regarded as an emergency condition that requires prompt treatment to avoid hospitalisation and to reduce morbidity and mortality. Rapid pre-hospital first-line treatment of convulsive status epilepticus is currently benzodiazepines, administered either by trained caregivers in the community (e.g. buccal midazolam, rectal diazepam) or by trained health professionals via intramuscular or intravenous routes (e.g. midazolam, lorazepam). There is a lack of clarity about the optimal treatment for convulsive status epilepticus in the pre-hospital setting.
OBJECTIVES
To assess the current evidence on the clinical effectiveness and cost-effectiveness of treatments for adults with convulsive status epilepticus in the pre-hospital setting.
DATA SOURCES
We searched major electronic databases, including MEDLINE, EMBASE, PsycInfo, CINAHL, CENTRAL, NHS Economic Evaluation Database, Health Technology Assessment Database, Research Papers in Economics, and the ISPOR Scientific Presentations Database, with no restrictions on publication date or language of publication. Final searches were carried out on 21 July 2020.
REVIEW METHODS
Systematic review of randomised controlled trials assessing adults with convulsive status epilepticus who received treatment before or on arrival at the emergency department. Eligible treatments were any antiepileptic drugs offered as first-line treatments, regardless of their route of administration. Primary outcomes were seizure cessation, seizure recurrence and adverse events. Two reviewers independently screened all citations identified by the search strategy, retrieved full-text articles, extracted data and assessed the risk of bias of the included trials. Results were described narratively.
RESULTS
Four trials (1345 randomised participants, of whom 1234 were adults) assessed the intravenous or intramuscular use of benzodiazepines or other antiepileptic drugs for the pre-hospital treatment of convulsive status epilepticus in adults. Three trials at a low risk of bias showed that benzodiazepines were effective in stopping seizures. In particular, intramuscular midazolam was non-inferior to intravenous lorazepam. The addition of levetiracetam to clonazepam did not show clear advantages over clonazepam alone. One trial at a high risk of bias showed that phenobarbital plus optional phenytoin was more effective in terminating seizures than diazepam plus phenytoin. The median time to seizure cessation from drug administration varied from 1.6 minutes to 15 minutes. The proportion of people with recurrence of seizures ranged from 10.4% to 19.1% in two trials reporting this outcome. Across trials, the rates of respiratory depression among participants receiving active treatments were generally low (from 6.4% to 10.6%). The mortality rate ranged from 2% to 7.6% in active treatment groups and from 6.2% to 15.5% in control groups. Only one study based on retrospective observational data met the criteria for economic evaluation; therefore, it was not possible to draw any robust conclusions on cost-effectiveness.
LIMITATIONS
The limited number of identified trials and their differences in terms of treatment comparisons and outcomes hindered any meaningful pooling of data. None of the included trials was conducted in the UK and none assessed the use of buccal midazolam or rectal diazepam. The review of economic evaluations was hampered by lack of suitable data.
CONCLUSIONS
Both intravenous lorazepam and intravenous diazepam administered by paramedics are more effective than a placebo in the treatments of adults with convulsive status epilepticus, and intramuscular midazolam is non-inferior to intravenous lorazepam. Large well-designed clinical trials are needed to establish which benzodiazepines are more effective and preferable in the pre-hospital setting.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42020201953.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in ; Vol. 26, No. 20. See the NIHR Journals Library website for further project information.
Topics: Adult; Anticonvulsants; Emergency Service, Hospital; Hospitals; Humans; Retrospective Studies; Status Epilepticus
PubMed: 35333156
DOI: 10.3310/RSVK2062 -
Current Neuropharmacology 2023Compelling evidence from preclinical and clinical studies supports the therapeutic role of cannabidiol (CBD) in several medical disorders. We reviewed the scientific...
BACKGROUND
Compelling evidence from preclinical and clinical studies supports the therapeutic role of cannabidiol (CBD) in several medical disorders. We reviewed the scientific evidence on CBD-related toxicity and adverse events (AEs) in 2019, at the beginning of the spike in clinical studies involving CBD. However, CBD safety remained uncertain.
OBJECTIVE
With the benefit of hindsight, we aimed to provide an update on CBD-related toxicity and AEs in humans.
METHODS
A systematic literature search was conducted following PRISMA guidelines. PubMed, Cochrane, and Embase were accessed in October 2022 to identify clinical studies mentioning CBDrelated toxicity/AEs from February 2019 to September 2022. Study design, population characteristics, CBD doses, treatment duration, co-medications, and AEs were compiled.
RESULTS
A total of 51 reports were included. Most studies investigated CBD efficacy and safety in neurological conditions, such as treatment-resistant epilepsies, although a growing number of studies are focusing on specific psychopathological conditions, such as substance use disorders, chronic psychosis, and anxiety. Most studies report mild or moderate severity of AEs. The most common AEs are diarrhea, somnolence, sedation, and upper respiratory disturbances. Few serious AEs have been reported, especially when CBD is co-administered with other classes of drugs, such as clobazam and valproate.
CONCLUSION
Clinical data suggest that CBD is well tolerated and associated with few serious AEs at therapeutic doses both in children and adults. However, interactions with other medications should be monitored carefully. Additional data are needed to investigate CBD's long-term efficacy and safety, and CBD use in medical conditions other than epilepsy syndromes.
Topics: Child; Adult; Humans; Cannabidiol; Epilepsy; Anxiety; Anticonvulsants
PubMed: 36946485
DOI: 10.2174/1570159X21666230322143401 -
BMC Veterinary Research May 2016The safety profile of anti-epileptic drugs (AEDs) is an important consideration for the regulatory bodies, owners and prescribing clinicians. Information on their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The safety profile of anti-epileptic drugs (AEDs) is an important consideration for the regulatory bodies, owners and prescribing clinicians. Information on their adverse effects still remains limited. A systematic review including a meta-analytic approach was designed to evaluate existing evidence for the safety profile of AEDs in canine patients. Electronic searches of PubMed, CAB Direct and Google scholar were carried out without date or language restrictions. Conference proceedings were also searched. Peer-reviewed full-length studies reporting adverse effects of AEDs in epileptic and healthy non-epileptic dogs were included. Studies were allocated to three groups based on their design. Individual studies were evaluated based on the quality of evidence (study design, study group sizes, subject enrolment quality and overall risk of bias) and the outcome measures reported (proportion of specific adverse effects for each AED, prevalence and 95% confidence interval of the affected population in each study and comparative odds ratio of adverse effects for AEDs).
RESULTS
Ninety studies, including six conference proceedings, reporting clinical outcomes of AEDs' adverse effects were identified. Few studies were designed as blinded randomised controlled clinical trials. Many studies included low canine populations with unclear criteria of subject enrolment and short treatment periods. Direct comparisons suggested that imepitoin and levetiracetam might have a better safety profile than phenobarbital, whilst the latter might have a better safety profile than potassium bromide. However, none of these comparisons showed a statistically significant difference. Comparisons between other AEDs were not possible as a considerable amount of studies lacked power calculations or adequate data to allow further statistical analysis. Individual AED assessments indicated that levetiracetam might be one of the safest AEDs, followed by imepitoin and then phenobarbital and potassium bromide; these findings were all supported by a strong level of evidence. The safety profile in other AEDs was variable, but weak evidence was found to permit firm conclusions or to compare their safety to other AEDs.
CONCLUSIONS
This systematic review provides objective evaluation of the most commonly used AEDs' adverse effects. Adverse effects usually appeared mild in all AEDs and subsided once doses and/or serum levels were monitored or after the AED was withdrawn. Although phenobarbital might be less safe than imepitoin and levetiracetam, there was insufficient evidence to classify it as an AED with a high risk of major adverse effects. It is important for clinicians to evaluate both AEDs' effectiveness and safety on an individual basis before the selection of the appropriate monotherapy or adjunctive AED therapy.
Topics: Animals; Anticonvulsants; Dogs; Epilepsy; Outcome and Process Assessment, Health Care
PubMed: 27206489
DOI: 10.1186/s12917-016-0703-y -
BMJ Clinical Evidence May 2008Simple febrile seizures are generalised in onset, last less than 15 minutes, and do not occur more than once in 24 hours. Complex seizures are longer lasting, have focal... (Review)
Review
INTRODUCTION
Simple febrile seizures are generalised in onset, last less than 15 minutes, and do not occur more than once in 24 hours. Complex seizures are longer lasting, have focal symptoms, and can recur within 24 hours. This review only deals with simple febrile seizures. About 2-5% of children in the USA and Western Europe, and 6-9% of infants and children in Japan, will have experienced at least one febrile seizure by the age of 5 years. Simple febrile seizures may slightly increase the risk of developing epilepsy, but have no known adverse effects on behaviour, scholastic performance, or neurocognition.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments given during episodes of fever in children with one or more previous simple febrile seizures? What are the effects of long-term (daily, for more than 1 month) anticonvulsant treatment in children with a history of simple febrile seizures? What are the effects of treatments on reducing the risk of subsequent epilepsy in children with a history of simple febrile seizures? We searched: Medline, Embase, The Cochrane Library and other important databases up to August 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticonvulsants (intermittent or continuous), and antipyretic treatments (physical antipyretic measures, paracetamol, ibuprofen).
Topics: Anticonvulsants; Epilepsy; Fever; Humans; Infant; Recurrence; Seizures, Febrile
PubMed: 19450310
DOI: No ID Found -
Expert Opinion on Pharmacotherapy Apr 2024Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy.
METHODS
A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone.
RESULTS
The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), = 0.99] compared to placebo.
CONCLUSION
Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile.
PROSPERO REGISTRATION NUMBER
CRD42023434883.
Topics: Humans; Anticonvulsants; Randomized Controlled Trials as Topic; Drug Resistant Epilepsy; Pregnanolone; Epilepsy; Treatment Outcome
PubMed: 38606458
DOI: 10.1080/14656566.2024.2342413 -
A systematic review and meta-analysis of heart rate variability in epilepsy and antiepileptic drugs.Epilepsia Feb 2012Epilepsy is associated with near-fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Epilepsy is associated with near-fatal and fatal arrhythmias, and sudden unexpected death in epilepsy (SUDEP) is partly related to cardiac events. Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, the results are still mixed regarding whether imbalance of sympathetic, vagal, or both systems is present in epilepsy, and also the importance of anticonvulsant treatment on the autonomic system. Therefore, we aimed to investigate epilepsy and its treatment impact on heart rate variability (HRV), assessed by sympathetic and parasympathetic activity expressed as low-frequency (LF) and high-frequency (HF) power spectrum, respectively.
METHOD
We performed a systematic review from the first date available to July 2011 in Medline and other databases; key search terms were "epilepsy"; "anticonvulsants"; "heart rate variability"; "vagal"; and "autonomous nervous system." Original studies that reported data and/or statistics of at least one HRV value were included, with data being extracted by two independent authors. We used a random-effects model with Hedges's g as the measurement of effect size to perform two main meta-analyses comparing LF and HF HRV values in (1) epilepsy patients versus controls; (2) patients receiving versus not receiving treatment; and (3) well-controlled versus refractory patients. Secondary analyses assessed other time- and frequency-domain measurements (nonlinear methods were not analyzed due to lack of sufficient data sets). Quality assessment of each study was verified and also meta-analytic techniques to identify and control bias. Meta-regression for age and gender was performed.
KEY FINDINGS
Initially, 366 references were identified. According to our eligibility criteria, 30 references (39 studies) were included in our analysis. Regarding HF, epilepsy patients presented lower values (g -0.69) than controls, with the 95% confidence interval (CI) ranging from -1.05 to -0.33. No significant differences were observed for LF (g -0.18; 95% CI -0.71 to 0.35). Patients receiving treatment presented HF values to those not receiving treatment (g -0.05; 95% CI -0.37 to 0.27), with a trend for having higher LF values (g 0.1; 95% CI -0.13 to 0.33), which was more pronounced in those receiving antiepileptic drugs (vs. vagus nerve stimulation). No differences were observed for well-controlled versus refractory patients, possibly due to the low number of studies. Regression for age and gender did not influence the results. Finally, secondary time-domain analyses also showed lower HRV and lower vagal activity in patients with epilepsy, as shown by the standard deviation of normal-to-normal interval (SDNN) and the root mean square of successive differences (RMSSD) indexes, respectively.
SIGNIFICANCE
We confirmed and extended the hypothesis of sympathovagal imbalance in epilepsy, as showed by lower HF, SDNN, and RMSSD values when compared to controls. In addition, there was a trend for higher LF values in patients receiving pharmacotherapy. As lower vagal (HF) and higher sympathetic (LF) tone are predictors of morbidity and mortality in cardiovascular samples, our findings highlight the importance of investigating autonomic function in patients with epilepsy in clinical practice. Assessing HRV might also be useful when planning therapeutic interventions, as some antiepileptic drugs can show hazardous effects in cardiac excitability, potentially leading to cardiac arrhythmia.
Topics: Anticonvulsants; Arrhythmias, Cardiac; Autonomic Nervous System; Death, Sudden; Epilepsy; Heart Rate; Humans
PubMed: 22221253
DOI: 10.1111/j.1528-1167.2011.03361.x -
Brain and Behavior Nov 2022To compare the efficacy and safety of Levetiracetam (LEV) and Oxcarbazepine (OXC) as monotherapy for the treatment of newly diagnosed focal epilepsy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety of Levetiracetam (LEV) and Oxcarbazepine (OXC) as monotherapy for the treatment of newly diagnosed focal epilepsy.
METHODS
We searched PubMed, Cochrane Library, EMBASE, and Google Scholar from January 1, 2000 to May 11, 2022, with no language restrictions along with The ClinicalTrials.gov website and the WHO International Controlled Trials Registry platforms. We pooled the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for the efficacy and safety outcomes. The quality of included trials was assessed using the Cochrane Collaboration's tool.
RESULTS
Two RCTs included a total of 574 newly diagnosed focal epilepsy patients (the LEV group [282 patients] and the OXC group [292 patients]). LEV group when compared with the OXC group had no significant difference in the pooled estimate of seizure freedom at week 24. (RR: 0.81; 95% CI: 0.62-1.05, p = .11). Similarly, there was no significant difference in the pooled estimate of withdrawal due to adverse events (AEs) (RR: 0.87; 95% CI: 0.34-2.23, p = .77). The commonly reported AEs in both trials were dizziness, headache, rash, somnolence, and nasopharyngitis with zero medication-related death and few serious AEs.
CONCLUSIONS
LEV is noninferior to OXC in terms of seizure freedom at week 24 and treatment withdrawal rate due to AEs among adults but long-term treatment data is still missing. Future multicentric double-blinded RCTs and real-world studies are of great need.
Topics: Adult; Humans; Oxcarbazepine; Levetiracetam; Anticonvulsants; Epilepsies, Partial
PubMed: 36184821
DOI: 10.1002/brb3.2779 -
Acta Neurologica Scandinavica Dec 2022There are about 10 million people with epilepsy (PWE) in China. In addition to therapies approved by the National Medical Products Administration, the use of... (Review)
Review
There are about 10 million people with epilepsy (PWE) in China. In addition to therapies approved by the National Medical Products Administration, the use of complementary and alternative medicine (CAM) is prevalent in Chines PWE. These CAM therapies mainly comprise traditional Chinese medicine herbs (TCMHs), acupuncture, and music. A retrospective literature search was performed to summarize the updates of CAM in China in the past ten years, and sixty-two papers were finally included. In this following review, we listed the animal and clinical studies to summarize the antiepileptic mechanisms and clinical efficacy of CAM in Chines PWE. The main mechanisms of TCMHs and acupuncture included regulation of neurotransmitters and receptors, voltage-gated ion channels modulation, expression of apoptosis-related genes, antioxidant response, and anti-inflammation. Although there were enormous clinical studies on them, the current available clinical trials were small, short-term, heterogeneous, and had a high risk of bias. With regard to music, a few studies conducted by Chinese scholars suggested that it was beneficial for PWE as an add-on therapy, which was consistent with the results of foreign studies. Further randomized clinical trials in large populations are required to prove the effectiveness and safety of CAM.
Topics: Humans; Retrospective Studies; Complementary Therapies; Epilepsy; Anticonvulsants; China
PubMed: 36082744
DOI: 10.1111/ane.13701 -
Seizure Oct 2020Status epilepticus (SE) is associated with high mortality and morbidity. Although SE is frequently seen in elderly patients, there is a lack of a cohesive report of... (Review)
Review
Status epilepticus (SE) is associated with high mortality and morbidity. Although SE is frequently seen in elderly patients, there is a lack of a cohesive report of outcome measures and associated factors within this population. Our aim was to systematically review studies reporting outcomes of SE among elderly patients and factors influencing these outcomes. A literature search was conducted in PubMed/MEDLINE, EMBASE, CINAHL Complete, and Cochrane Library from database conception to April 22, 2018. A total of 85 studies were included in this systematic review. The included studies show that mortality is higher in elderly patients than in adult patients. Lesional etiologies, higher number of comorbidities, NCSE, RSE, longer hospital and intensive care unit stays, and infection during hospitalization are associated with poor outcome. Future studies should consider measuring functional outcomes, comparative studies between elderly and adults and AED clinical trials specific for elderly with SE.
Topics: Adult; Aged; Anticonvulsants; Comorbidity; Humans; Intensive Care Units; Retrospective Studies; Status Epilepticus
PubMed: 32862117
DOI: 10.1016/j.seizure.2020.08.021 -
Neuropsychology Review Dec 2016Psychiatric disorders and associated poor psychosocial outcomes are recognised to be a common sequelae of epilepsy. The extent to which this is true of genetic... (Review)
Review
Psychiatric disorders and associated poor psychosocial outcomes are recognised to be a common sequelae of epilepsy. The extent to which this is true of genetic generalised epilepsies (GGE), particularly syndromes other than juvenile myoclonic epilepsy (JME) is unclear. This systematic review synthesises findings regarding psychiatric and associated comorbidities in adults and children with GGE. Systematic review yielded 34 peer-reviewed studies of psychiatric and psychosocial outcomes in adults and children with GGE. Clinically significant psychiatric comorbidity was reported in over half of all children and up to a third of all adults with GGE. There was no evidence to support the presence of personality traits specific to JME or other syndromes; rather rates mirrored community samples. A small number of studies report poor psychosocial outcomes in GGE, however the interpretation of these findings is limited by paucity of healthy comparison groups. Some evidence suggests that anti-epileptic drug polytherapy in children and seizure burden at all ages may constitute risk factors for psychopathology. Findings highlight the importance of early screening so as not to overlook early or developing symptoms of psychopathology.
Topics: Anticonvulsants; Comorbidity; Epilepsy, Generalized; Humans; Mental Disorders
PubMed: 27726043
DOI: 10.1007/s11065-016-9333-1